medwireNews: Girls with central precocious puberty (CPP) or early and fast puberty (EFP) benefit from the addition of recombinant human growth hormone (rhGH) to gonadotropin-releasing hormone analogues (GnRHa) but the combination should not be routinely recommended, researchers report.

Junfen Fu (Children’s Hospital of Zhejiang University School of Medicine, Hangzhou, China) and co-investigators say that although the greatest long-term height gains were achieved with the combination treatment, there is still a proportion of patients who do not have a satisfactory outcome (ie, <5 cm height gained).

This knowledge, along with the high cost of combination treatment and a “lack of large-scale randomized controlled trials demonstrating its safety and efficacy,” led them to agree with the Pediatric Endocrinology Society and the European Society for Paediatric Endocrinology that “the combination of GnRHa and rhGH is not recommended as a routine therapy.”

The researchers’ conclusions are based on a retrospective analysis of data for 448 Chinese girls with CPP or EFP who received GnRHa and rhGH (n=118), GnRHa alone (n=276) or no treatment (n=54) at 12 children’s hospitals in China between 1998 and 2017. When used, rhGH was given in a dose of 0.1–0.2 U/kg per day up to the age of 11.0–11.5 years.

The team found that the girls who received GnRHa plus rhGH had significantly greater mean height gain (final adult height–predictive adult height) than those who received GnRHa alone, at 9.51 versus 8.07 cm, respectively, with both groups gaining more height than the no treatment group, at 6.44 cm.

A similar pattern was observed for genetic height gain (final adult height–target height), with mean gains of 4.0 and 2.0 cm for the GnRHa plus rhGH group and GnRHa groups, respectively, while individuals in the control group had no genetic height gain but reached their target height.

In addition, a greater proportion of patients in the GnRHa plus rhGH group than in the GnRHa group achieved a satisfactory height gain of at least 5 cm (75.8 vs 69.7%).

Factors that best predicted the treatment effect of GnRHa on receiver operating characteristic curve analysis were loss in height potential, predicted adult height at baseline, baseline height/height based on bone age, age based on height/height based on bone age, and degree of height loss.

Using an equation incorporating these parameters, the researchers correctly identified 93.3% and 90.9% of patients who achieved at least a 5 cm gain in height while receiving GnRHa plus rhGH and GnRHa alone, respectively.

Writing in The Journal of Clinical Endocrinology & Metabolism, Fu and co-authors conclude that although not routinely recommended, “the combined treatment may be beneficial for female CPP/EFP patients with low predicted heights and a greater degree of [bone age] advancement.”

By Laura Cowen

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J Clin Endocrinol Metab 2019; doi:10.1210/clinem/dgz027